Co-expression of Bcl-2 protein and vascular endothelial growth factor in hepatocellular carcinomas treated by chemoembolization

Liver. 1999 Feb;19(1):25-31. doi: 10.1111/j.1478-3231.1999.tb00005.x.

Abstract

Aims/background: Transcatheter arterial chemoembolization (TAE) of hepatocellular carcinoma (HCC) causes anoxia. Escape of cancer cells from anoxic injury may be enhanced by induction of proteins which provide resistance to apoptosis.

Methods: We examined HCCs immunohistochemically for Bcl-2, vascular endothelial growth factor (VEGF), p53, and Ki67. The staining intensity for VEGF, a protein induced by anoxia, was assessed morphometrically with a computer-assisted image-analyzer.

Results: The frequency of Bcl-2 positive cells was higher in HCCs that had undergone TAE (TAE HCC) than that in HCCs that had not undergone TAE (41.75+/-15.06 vs. 1.01+/-0.79 cells/1000 cells, p = 0.0173). The frequency of p53- or Ki67-positive cells was not increased after TAE. Of 12 TAE HCCs, 7 had Bcl-2 positive HCC cells and 6 had clusters of Bcl-2 positive cells. In contrast, 2 of 11 HCCs that had not undergone TAE had only a few, sporadically distributed, Bcl-2-positive cells. The staining intensity for VEGF was higher in Bcl-2 positive than in Bcl-2 negative areas (1.208+/-0.091 vs. 1.071+/-0.017, p = 0.0222). Furthermore, the VEGF staining intensity in Bcl-2 positive areas of TAE HCCs was higher than in Bcl-2 negative areas (1.296+/-0.126 vs. 1.066+/-0.024, p = 0.0186), while in HCCs that had not undergone TAE the staining intensity was similar.

Conclusions: TAE of HCC can induce Bcl-2 expression, possibly through anoxic stress.

MeSH terms

  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / therapy
  • Cell Hypoxia
  • Chemoembolization, Therapeutic*
  • Endothelial Growth Factors / metabolism*
  • Female
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / metabolism
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / therapy
  • Lymphokines / metabolism*
  • Male
  • Middle Aged
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Tumor Suppressor Protein p53 / metabolism
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Substances

  • Endothelial Growth Factors
  • Ki-67 Antigen
  • Lymphokines
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Suppressor Protein p53
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors